Search bioRxiv⌕ Search

Biology subjects

Lemaire, L. A.

Publications and source records attributed to Lemaire, L. A..

3 recordsLinked to original sources

Allele-Resolved Hybrid Embryos Reveal the Fates of Regulatory Divergence

Developmental programs can remain conserved despite extensive regulatory divergence, but how evolved regulatory differences are transmitted through embryonic lineages remains unclear. Here we generate a time resolved, allele resolved single-cell atlas of hybrid embryogenesis between Ciona intestinalis and Ciona savignyi, enabling regulatory differences accumulated between species to be followed across defined developmental lineages. We find that allelic differences are maintained or remodeled in lineage specific ways, with their outcomes associated with regulatory origin and allele specific chromatin accessibility. Across multiple tissues, allelic divergence increases along gene regulatory network (GRN) hierarchy from upstream regulators toward downstream regulators and effector genes. In the cardiopharyngeal lineage, Foxf illustrates how allelic dominance provides partial compensation for highly divergent regulatory sequences and thereby contributes to developmental system drift. Together, our results reveal that regulatory divergence is dynamically sorted during development according to lineage context and GRN hierarchy. This lineage resolved framework provides a developmental basis for understanding how extensive regulatory evolution can accumulate while conserved embryonic programs are maintained.

developmental biology↗

Temporal Gatekeeping Role of Lmx1 during chordate neural tube morphogenesis

Neural tube closure is a critical developmental process, essential to the proper formation of the vertebrate nervous system. This process starts with the invagination of neural plate cells. Its borders then converge, leading to the closure of the neural tube, propagating like a zipper. Afterwards, cell intercalation and proliferation allow the tube to elongate. Neural tube closure involves thousands of cells in vertebrates. However, the closest invertebrates to vertebrates, the tunicates, such as Ciona, close a hollow dorsal neural tube with fewer than 20 neural cells. This minimal model makes it easier to study the mechanisms of this intricated process. In Ciona, the transcription factor Lmx1 is expressed in the most dorsal cells of the developing neural tube, like its vertebrate orthologs. In vertebrates, Lmx1 paralogs are involved in neural tube patterning. However, no function related to morphogenesis has been uncovered. Here, we explore Ciona Lmx1 roles during neural tube closure. Lmx1 Knockdown leads to slight but significant defects in neural tube closure. The overexpression of a repressive Lmx1 variant prevents the proper intercalation of the dorsal neural tube cells, impeding the anterior progression of the zipper. Furthermore, studies of Lmx1 regulatory sequences indicate that Pax3/7, ZicL, and Nodal signaling may directly regulate its transcription. These transcription factors are present at the vertebrate neural plate border, suggesting that Lmx1 regulation is conserved across chordates. It raises the possibility of an unrecognized role for Lmx1 during vertebrate neural tube morphogenesis. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=187 SRC="FIGDIR/small/709676v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@f409b1org.highwire.dtl.DTLVardef@1a88180org.highwire.dtl.DTLVardef@1ce2a89org.highwire.dtl.DTLVardef@4aba89_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

A pair-rule-like transcription network coordinates neural tube closure in a proto-vertebrate

Neural tube closure (NTC) is a conserved morphogenetic process in chordates, during which the neural plate folds and fuses to form a closed neural tube. While the mechanical forces and signaling pathways governing NTC have been characterized in vertebrates, the transcriptional programs coordinating cell behaviors during closure remain less understood. Here, we identify a transcriptional circuit involving Lmx1, Cdkn1b, and Msx that regulates dorsal midline dynamics during NTC in the tunicate Ciona. High-resolution HCR in situ hybridization reveals that Lmx1 is dynamically enriched at the zippering point and advances in a posterior-to-anterior transcription wave, while Msx is downregulated in the same region, marking a transition from early neural patterning to morphogenetic execution. As closure progresses, Lmx1 and Cdkn1b exhibit complementary, alternating expression at the dorsal midline, resembling a pair-rule-like pattern. Misexpression studies show that Lmx1 promotes proliferation and activates its own expression, whereas Cdkn1b limits proliferation and impedes closure. Single-cell RNA-seq reveals transcriptionally distinct dorsal neural populations enriched for Lmx1 or Cdkn1b, supporting spatially organized cell-cycle states. These findings suggest that a transcriptional switch from Msx to Lmx1, followed by spatially alternating Lmx1 and Cdkn1b activity, coordinates proliferation and neural fold fusion during NTC. This mechanism may represent a general strategy for regulating epithelial remodeling in animal embryos.

developmental biology↗