Ivan Moskowitz, MD, PhD (University of Chicago): “A Consideration of Time: Hedgehog-signaling-dependent Heterochronic Control of Complex Organ Development”
April 4, 2025
11:00 AM - 12:00 PM
Location
Moss Auditorium - 1020 COMRB
Calendar
Download iCal FileHost: Dharma Pally, PhD and Leanna Leverton
Organ development requires tightly controlled stage-specific differentiation of progenitor cells. We propose a heterochronic paradigm that the explicit molecular control of differentiation timing, independent of other developmental mechanisms such as cell fate determination or patterning, is essential for complex organ morphogenesis and the avoidance of birth defects. Pioneering work by Ambros and Horvitz identified heterochronic mutants in the nematode C. elegans that caused altered differentiation timing independent of cell fate or patterning decisions, implicating molecular differentiation timers. In contrast, explicit heterochronic mechanisms that control differentiation timing in mammals remain poorly defined.
We have recently implicated Hedgehog signaling as a heterochronic modulator of mammalian cardiac and neuronal progenitor differentiation timing. Our recent work investigates: (1) the relationship between altered Hedgehog signaling, disrupted progenitor differentiation timing, and organ morphogenesis; (2) the Hedgehog signaling-dependent molecular and genomic mechanisms controlling progenitor differentiation timing; and (3) the extent to which Hedgehog signaling acts as a progenitor differentiation control mechanism in diverse contexts.
Reference: Rowton et al. Hedgehog signaling activates a heterochronic gene regulatory network to control differentiation timing across lineages. Developmental Cell. 2022 Sep 26;57(18):2181-2203. doi: 10.1016/j.devcel.2022.08.009. PMID: 36108627
Date posted
Jan 8, 2025
Date updated
Apr 3, 2025
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