Skeletal element elongation and interdigital tissue regression in developing bat limbs: a gene expression analysis

Vertebrate limbs classically illustrate the morphological diversity of homologous structure. Bat limbs exemplify this, having strikingly divergent limbs: wings with asymmetrically elongated digit elements, supporting expansive membranes; and hindlimbs with short, symmetrical, free digits. An understanding of the genes, interactions and events that shape bat limbs, will inform conventional models of development. This dissertation characterised differential expression of Meis2, in the context of interdigital regression, and the 5'HoxD genes in the context of digit formation in developing bat autopods (CS15 - CS18). Meis2 is involved in limb proximodistal patterning, and has been shown to promote proliferation, and survival of cells in other developmental contexts. Meis2 had strong expression in the expanding bat forelimb interdigits, with lowered expression in mouse and bat hindlimb interdigits, and did not correspond with Hoxa13 expression, which was reduced in the forelimb. Autopod expression was independent of retinoic acid (RA) signalling, with genes involved in RA synthesis ( Rdh10 , Aldha2 ) , degradation ( Cyp26b1 ) and signalling (Rar β) expressed in bat limbs. Altered expression patterns of Aldha2 and Cyp26b1, indicate that this pathway may be modulated in the forelimb. Meis2 is suggested to play a role in interdigital tissue retention, enhancing cell proliferation and contributing to wing expansion. 5'HoxD genes (Hoxd10 - 13) are involved in limb patterning, digit formation and growth. Their modular autopod expression domains correspond to the bat skeletal element phenotype, with strong overexpression of Hoxd10 - 11 (and to a lesser extent Hoxd12) in the forelimb posterior elements (digits II - V), which are highly elongated, and a loss of expression of these genes in hindlimb digits. These genes were not expressed in a typical reverse collinear relationship, with absolute q PCR revealing highest expression of Hoxd10. While the coding protein sequence of these genes appeared highly conserved between bats and other mammals, several changes were found in the CsC region of the digit enhancer Prox, some of which were associated with alterations in transcription binding sites. These findings indicate that Hoxd10 - 12 expressions contribute to the altered skeletal element morphologies of bat forelimbs and hindlimbs. This study makes a valuable contribution to the growing body of work that explores bat limb development and the evolutionary adaptation s of these unique structures.

Grantor dc:publisher.institution

Department of Molecular and Cell Biology

Year dc:date.issued

2016

Author dc:creator

• Mason, Mandy K

Advisors dc:contributor.advisor

• Illing, Nicola
• Jacobs, David S

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/11427/20293

OAI identifier oai:identifier

oai:open.uct.ac.za:11427/20293