Understanding digit patterning and evolution across amniotes

Positional information is a fundamental principle in embryonic development. It describes how cells interpret the concentration of signalling molecules to acquire positional values, which are then interpreted into distinct morphological outcomes. In the classic model, a Sonic hedgehog (Shh) signalling gradient specifies the positional values of the three chick wing digits and four chick leg digits by acting as a morphogen. However, recent work on the mouse limb with five digits suggests that Shh does not act as a morphogen, but instead acts through undefined secondary signalling molecules.
In this proposal, we will build upon two major recent advances from our lab:
1) The development of a mammalian-like pentadactyl chick leg model: The chick leg has a phalangeal count in its four digits that has remained stable for over 350 million years. We have developed a chick leg model with five digits that has a mammalian phalangeal count, which can give insights into the underlying mechanisms that caused evolutionary changes in amniote digit patterning.
2) The discovery of a Shh-Bmp2-p27Kip1 pathway in the chick wing: This pathway plays a key role in specifying the identity of digit 3 and inhibiting posterior digit formation, potentially explaining key differences between mammalian and avian digit patterning.
We will characterise the digits of the pentadactyl chick leg model to understand how closely they resemble mammalian digit identities. To do this, we will compare the transcriptomic profiles of the digits in normal and mammalianised chick legs with those of mouse hindlimbs, focussing on transcription factors and signalling proteins potentially involved in determining digit identity.
We will investigate the involvement of the Shh-Bmp2-p27kip1 pathway in determining digit number in the chick leg and explore whether different Bmp proteins specify its distinct digit identities. We will also determine if this pathway is expressed in the mouse limb to understand if its...