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Title: Limb initiation across tetrapods
Abstract: The earliest stage in limb development is limb initiation, where the limb progenitors are specified and limb proliferation and outgrowth begin. Limb initiation has been well characterised in the mouse and the chick, but limb initiation in non-amniote model systems has been less well studied. Also, while we know much about the fate of limb progenitors (LPs), only recently have genes been identified which are sufficient to confer a LP-like state onto fibroblasts. We sought to investigate these two strands of inquiry, to further understand limb initiation from a number of perspectives.
For our first vignette, we investigated the mode of limb initiation in X. laevis, finding that the formation of the hindlimb bud more closely resembles the convergent migration of Tbx5+ cells seen in zebrafish than the EMT observed in amniote limb initiation. This has implications for the evolutionary history of limb initiation.
Our second line of inquiry sought to determine whether Evi1 was functionally redundant with Prdm16 in specifying limb progenitors in the mouse. Prdm16 had been shown to be sufficient to induce a LP-like state in fibroblasts, in concert with Zbtb16 and Lin28a. We showed that most Evi1 isoforms were able to substitute for Prdm16 in vitro, suggesting functional redundancy between these genes.
Committee: Cliff Tabin (Advisor, Harvard Medical School), Jim Hanken (Co-advisor), Elena Kramer, Mansi Srivastava, John Young (Simmons)