Year: 2014
Type: dissertation
Abstract: Limb skeletal pattern heavily relies on graded Sonic hedgehog (Shh) signaling. As a morphogen and growth cue, Shh regulates identities of posterior limb elements including the ulna/fibula and digits 2 through 5. In contrast, proximal and anterior structures including the humerus/femur, radius/tibia and digit 1 are regarded as Shh-independent and the mechanisms governing their pattern formation are unclear. Here I show that patterning of the proximal and anterior limb skeleton involves an early specification phase dependent on two transcription factors, Irx3 and Irx5 (Irx3/5). They are expressed in the anterior margin of the limb field to regulate expression of the key anterior prepattern gene Gli3 and specify the anterior population during limb initiation. The early specification phase is followed by a late modulation phase during which Shh signaling negatively regulates these anterior elements. In addition, Irx3/5 also play a role in limb bud morphogenesis. Irx3/5-DKO hindlimb buds are small with abnormal shape due to prolonged cell cycle time and division defects including anaphase bridge and altered cell division orientation in the anterior hindlimb field. Therefore, pattern formation of anterior limb skeletal elements requires functions of Irx3/5 during limb bud initiation for the specification and expansion of anterior population followed by negative modulation by Shh signaling.
Source: TSpace (University of Toronto)
Author: Li, Danyi
Institution: University of Toronto
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2763530934