Abstract

Name: Meng Zhu Affiliation: Tabin lab, Harvard University

Title: Maternal oxygen levels regulate the timing of limb development in amniote species

Abstract:

Heterochrony, or the alternation of developmental timing, is an important mechanism underlying changes during evolution. A notable example involves the timing of amniote limb formation, where avian species display synchronized growth of the forelimbs and hindlimbs, while mammalian species show a marked delay in hindlimb development relative to forelimb. This is hypothesized to have evolved in the context of an energy trade-off involving constrained nutrient supplies in the early development of eutherian mammals, yet the molecular basis of the delay is poorly understood. We here show that mammalian limb heterochrony is evident from the time the limb buds are first initiated, and is associated with heterochronic expression of T-box transcription factors. This heterochronic change relative to non-mammalian embryos is not due to changes in cis-regulatory elements controlling T-box gene suppression, but unexpectedly, is regulated by the differential oxygen levels to which avian and mammalian embryos are exposed at prelimb initiation stages. By integrating RNA -sequencing analyses with genetic assays, we found that hypoxia’s impact on hindlimb development is at least partially mediated through the expression of NFKB transcription factor, cRel. Taken together, these results provide mechanistic understanding of an important example of developmental heterochrony and exemplify the importance of the maternal environment in regulating the timing of embryonic development. In addition, our results help to explain the limb-type specific venerability to gestational hypoxia.

Name: Alex Plum Affiliation: University of California San Diego (Biophysics PhD student)

Title: Morphogen patterning in dynamic tissues

Abstract:

Embryogenesis integrates morphogenesis—coordinated cell movements—with cell differentiation, often informed by morphogen patterning. While largely studied independently, morphogenesis and patterning often unfold simultaneously in early embryos. Yet how cell movements affect morphogen transport and cells’ exposure over time remains unclear, as most pattern formation models assume static tissues. Here we develop a theoretical framework for morphogen patterning in dynamic tissues,

recasting advection-reaction-diffusion equations in the cells’ moving reference frames. This framework (i) elucidates how morphogenesis mediates morphogen transport and compartmentalization: cell-cell diffusive transport is enhanced at multicellular flow attractors, while repellers act as barriers, affecting cell fate induction and bifurcations. (ii) It formalizes cell-cell signaling ranges in dynamic tissues, deconfounding morphogenetic movements to identify which cells could communicate via morphogens. (iii) It provides two new nondimensional numbers to assess when and where morphogenesis affects morphogen transport. We demonstrate this framework by analyzing classical patterning models with common morphogenetic motifs as well as experimental tissue flows. Our work rationalizes dynamic tissue patterning in development, constraining candidate patterning mechanisms and parameters using accessible cell motion data.