Bat wing development
Encyclopedia
The order Chiroptera , comprising all bats, has evolved the unique mammalian adaptation of flight. Bat wings are modified tetrapod
forelimbs. Because bats are mammals, the skeletal structures in their wings are morphologically homologous to the skeletal components found in other tetrapod forelimbs. Through adaptive evolution these structures in bats have undergone dramatic morphological changes. This evolutionary innovation involved many morphological changes such as webbed digits, elongation of the forelimb, and reduction in bone thickness. Recently, there have been comparative studies of mouse and bat forelimb development to understand the genetic basis of morphological evolution. Consequently, the bat wing is a valuable evo-devo model for studying the evolution of vertebrate limb diversity.
involves many signaling molecules such as FGF
, BMP
, SHH
and WNT
. The apical ectodermal ridge is a structure found at the distal most tip which becomes a key signaling center for the developing limb. Surprisingly many of the same signaling pathways known to play a role in tetrapod limb development have been found to play a role in Bat forelimb development but the timing, intensity, and spatial gene expression
of some orthologous genes have changed. Since mice are also mammals, it is convenient to compare morphology and development of forelimbs between mice and bats; these comparisons may elucidate the genetic basis of adaptive bat wing development.
Although many of the molecular mechanisms involved in limb development are conserved between mouse and bat, there are a number of differences primarily seen in gene expression patterns. Surprisingly, the coding regions of many of these genes with different expression domains are highly conserved between mouse and bat. Thus, it is likely that this major morphological transition was a consequence of cis-regulatory changes. Researchers can study the genetic basis of bat wing development by using comparative in situ hybridization
to examine gene expression domains and using experimental embryology in mice and bats.
) allowed a greater surface area of the wing necessary for flight. All vertebrate limb formation initially has tissue between the digits after which apoptosis occurs to separate the digits. BMP signals are most likely responsible for the interdigit apoptosis as they are expressed in the interdigit tissue and blocking BMP signaling will prevent interdigital apoptosis
. However, in bats, BMP genes are still expressed in the interdigits and yet interdigit apotosis is repressed. FGF signaling has been associated with blocking cell death. Interestingly, fgf8
is expressed in bat interdigit tissue during a time when apoptosis occurs which does not occur in mice. Thus, FGFs may play a role in blocking the apoptotic effects of BMPs in the bat wing interdigit. Finally, applying ectopic BMPs and FGF antagonists to developing bat wings results in apoptosis of the patagium.
, which encodes a transcription factor. The expression patterns of prx1 in bats differs from mice in that prx1 has an expanded expression domain and is upregulated.
Researchers found that the coding region of prx1 in bats is nearly identical to mice but found a bat-specific prx1 enhancer
. When they replaced the bat prx1 enhancer with the endogenous enhancer found in mice, these transgenic mice had slightly increased forlimbs. Comparative studies have established that bat digits undergo a more rapid rate of chondrocyte
proliferation. In addition to interdigit apoptosis, BMPs have been shown to affect chrondrocyte proliferation and digit length in mice. Bmp-2
shows increased expression in the digits of bats compared with mice, suggesting that a change in the BMP pathway has occurred to give rise to longer bat digits.
is reduced in width and fused to the other zeugopod element, the radius. One of the possible molecular pathways involved in reduction of bat skeletal forelimb thickness is differences in SHH
expression. Mice with shh null mutations lose their ulna structure. Another good candidate for bat bone reduction is Hox-d13
, a gene belonging to the Hox gene family. In situ hybridization studies have found that the Hoxd13 expression domain in bat limbs has been shifted posteriorly in comparison to mouse. This observed difference in the expression pattern of Hoxd13 may also explain reduced size and density of the ulna found in bats. Overall, these studies suggest that the molecular changes responsible for the evolution of wings in bats is due to genetic regulatory changes.
Tetrapod
Tetrapods are vertebrate animals having four limbs. Amphibians, reptiles, birds and mammals are all tetrapods; even snakes and other limbless reptiles and amphibians are tetrapods by descent. The earliest tetrapods evolved from the lobe-finned fishes in the Devonian...
forelimbs. Because bats are mammals, the skeletal structures in their wings are morphologically homologous to the skeletal components found in other tetrapod forelimbs. Through adaptive evolution these structures in bats have undergone dramatic morphological changes. This evolutionary innovation involved many morphological changes such as webbed digits, elongation of the forelimb, and reduction in bone thickness. Recently, there have been comparative studies of mouse and bat forelimb development to understand the genetic basis of morphological evolution. Consequently, the bat wing is a valuable evo-devo model for studying the evolution of vertebrate limb diversity.
Comparisons to mouse limb development
Tetrapod limb developmentLimb development
Limb development in tetrapods — animals with four limbs — is an area of active research in developmental biology. Limb formation begins in the limb field, as a limb "bud." Fibroblast growth factor induces formation of an organizer, called the apical ectodermal ridge , which guides further...
involves many signaling molecules such as FGF
FGF
FGF may refer to:* Federación Gallega de Fútbol, the governing body of the sport of football in Galicia, Spain* Fédération Guinéenne de Football, the governing body of football in Guinea...
, BMP
BMP
-In computing:* BMP file format, the file name extension for the Bitmap image file format.* Basic Multilingual Plane, related to the Unicode character set.* Beep Media Player, a multimedia player.-Biology:...
, SHH
SHH
SHH can refer to:* Summer Heights High, an Australian TV series* Sonic hedgehog, an important protein during vertebrate organogenesis* Students Helping Honduras, an international non-governmental organization operating in the U.S. and Honduras...
and WNT
WNT
WNT is a three-letter abbreviation with multiple meanings, as described below:*Windows NT*WNT *Wnt signaling pathway, a complex protein network...
. The apical ectodermal ridge is a structure found at the distal most tip which becomes a key signaling center for the developing limb. Surprisingly many of the same signaling pathways known to play a role in tetrapod limb development have been found to play a role in Bat forelimb development but the timing, intensity, and spatial gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
of some orthologous genes have changed. Since mice are also mammals, it is convenient to compare morphology and development of forelimbs between mice and bats; these comparisons may elucidate the genetic basis of adaptive bat wing development.
Although many of the molecular mechanisms involved in limb development are conserved between mouse and bat, there are a number of differences primarily seen in gene expression patterns. Surprisingly, the coding regions of many of these genes with different expression domains are highly conserved between mouse and bat. Thus, it is likely that this major morphological transition was a consequence of cis-regulatory changes. Researchers can study the genetic basis of bat wing development by using comparative in situ hybridization
In situ hybridization
In situ hybridization is a type of hybridization that uses a labeled complementary DNA or RNA strand to localize a specific DNA or RNA sequence in a portion or section of tissue , or, if the tissue is small enough , in the entire tissue...
to examine gene expression domains and using experimental embryology in mice and bats.
Presence of webbed digits
Formation of the bat wing membrane (the patagiumPatagium
*In bats, the skin forming the surface of the wing. It is an extension of the skin of the abdomen that runs to the tip of each digit, uniting the forelimb with the body.*The patagium of a bat has four distinct parts:...
) allowed a greater surface area of the wing necessary for flight. All vertebrate limb formation initially has tissue between the digits after which apoptosis occurs to separate the digits. BMP signals are most likely responsible for the interdigit apoptosis as they are expressed in the interdigit tissue and blocking BMP signaling will prevent interdigital apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
. However, in bats, BMP genes are still expressed in the interdigits and yet interdigit apotosis is repressed. FGF signaling has been associated with blocking cell death. Interestingly, fgf8
FGF
FGF may refer to:* Federación Gallega de Fútbol, the governing body of the sport of football in Galicia, Spain* Fédération Guinéenne de Football, the governing body of football in Guinea...
is expressed in bat interdigit tissue during a time when apoptosis occurs which does not occur in mice. Thus, FGFs may play a role in blocking the apoptotic effects of BMPs in the bat wing interdigit. Finally, applying ectopic BMPs and FGF antagonists to developing bat wings results in apoptosis of the patagium.
Elongation of forelimb
One major difference in bat forearms is that their skeletal limb structures are elongated. This elongation of the forelimb skeleton is required to support the wing membrane. Comparative in situ hybridization studies have revealed that the expression domain of fgf8 in bat forelimb AER are expanded in comparison to the mouse forelimb, suggesting that expanded expression of fgf8 may contribute to the larger size of the bat forelimb. Because the mouse and bat orthologs are conserved, there is likely to be a regulatory change in fgf8. In mice, one gene known to regulate limb growth is prx1PRX (gene)
Periaxin is a protein that in humans is encoded by the PRX gene.-External links:*...
, which encodes a transcription factor. The expression patterns of prx1 in bats differs from mice in that prx1 has an expanded expression domain and is upregulated.
Researchers found that the coding region of prx1 in bats is nearly identical to mice but found a bat-specific prx1 enhancer
Enhancer (genetics)
In genetics, an enhancer is a short region of DNA that can be bound with proteins to enhance transcription levels of genes in a gene cluster...
. When they replaced the bat prx1 enhancer with the endogenous enhancer found in mice, these transgenic mice had slightly increased forlimbs. Comparative studies have established that bat digits undergo a more rapid rate of chondrocyte
Chondrocyte
Chondrocytes are the only cells found in cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans...
proliferation. In addition to interdigit apoptosis, BMPs have been shown to affect chrondrocyte proliferation and digit length in mice. Bmp-2
Bone morphogenetic protein 2
Bone morphogenetic protein 2 or BMP-2 belongs to the TGF-β superfamily of proteins.-Function:BMP-2 like other bone morphogenetic proteins, plays an important role in the development of bone and cartilage. It is involved in the hedgehog pathway, TGF beta signaling pathway, and in cytokine-cytokine...
shows increased expression in the digits of bats compared with mice, suggesting that a change in the BMP pathway has occurred to give rise to longer bat digits.
Reduction in bone thickness
Another major difference in bat forelimbs is in the density of their skeletal limbs. The bones found in their forelimbs are reduced to achieve a light body weight required for flight. In particular, their ulnaUlna
The ulna is one of the two long bones in the forearm, the other being the radius. It is prismatic in form and runs parallel to the radius, which is shorter and smaller. In anatomical position The ulna is one of the two long bones in the forearm, the other being the radius. It is prismatic in form...
is reduced in width and fused to the other zeugopod element, the radius. One of the possible molecular pathways involved in reduction of bat skeletal forelimb thickness is differences in SHH
SHH
SHH can refer to:* Summer Heights High, an Australian TV series* Sonic hedgehog, an important protein during vertebrate organogenesis* Students Helping Honduras, an international non-governmental organization operating in the U.S. and Honduras...
expression. Mice with shh null mutations lose their ulna structure. Another good candidate for bat bone reduction is Hox-d13
HOXD13
Homeobox protein Hox-D13 is a protein that in humans is encoded by the HOXD13 gene.This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms...
, a gene belonging to the Hox gene family. In situ hybridization studies have found that the Hoxd13 expression domain in bat limbs has been shifted posteriorly in comparison to mouse. This observed difference in the expression pattern of Hoxd13 may also explain reduced size and density of the ulna found in bats. Overall, these studies suggest that the molecular changes responsible for the evolution of wings in bats is due to genetic regulatory changes.