Biology subjects

Martik, M. L.

Publications and source records attributed to Martik, M. L..

3 recordsLinked to original sources

bioRxiv2025

Ectomesenchymal identity emerges via relief of Twist1transcript destabilization

During vertebrate development, cranial neural crest cells (CNCCs) differentiate into a variety of derivatives, including ectodermal cell types (neurons, glia, and pigment cells) as well as a suite of derivatives that are classically associated with the mesoderm (cartilage, bone and muscle) and are collectively termed ectomesenchyme. While the molecular decisions that guide CNCCs toward ectomesenchymal identity remain incompletely understood, the transcription factor Twist1 plays a central role. Here, we investigate the regulation of Twist1 expression in CNCCs and find that Twist1 is expressed by late migratory ectomesenchymal CNCCs in Gallus gallus and Danio rerio embryos. Using Hi-ChIP, ATAC-seq, and CUT&RUN sequencing data, we identify a distal enhancer for Twist1 within the Hdac9 locus that is active in the neural tube and CNCCs. Notably, this enhancer is directly bound by TFAP2 transcription factors and is active in pre-migratory CNCCs, a stage when Twist1 transcripts are not detectable in CNCCs. We reconcile this temporal discrepancy by showing that the Twist1 3 UTR of multiple vertebrate species (but not the non-vertebrate chordate Ciona intestinalis) is sufficient to destabilize GFP transcripts in the neural tube and surface ectoderm. Together, these findings reveal a vertebrate-specific, two-tiered regulatory mechanism that uncouples enhancer activity from transcript accumulation, gating the onset of Twist1 expression in CNCCs and the acquisition of ectomesenchymal identity in vertebrate CNCCs.

developmental biology↗

bioRxiv2025

Reactivation of an Embryonic Cardiac Neural Crest Transcriptional Subcircuit During Zebrafish Heart Regeneration

During vertebrate development, the heart primarily arises from mesoderm, with crucial contributions from cardiac neural crest cells that migrate to the heart and form a variety of cardiovascular derivatives. Here, by integrating bulk and single cell RNA-seq with ATAC-seq, we identify a gene regulatory subcircuit specific to migratory cardiac crest cells composed of key transcription factors egr1, sox9a, tfap2a and ets1. Notably, we show that cells expressing the canonical neural crest gene sox10 are essential for proper cardiac regeneration in adult zebrafish. Furthermore, expression of all transcription factors from the migratory cardiac crest gene subcircuit are reactivated after injury at the wound edge. Together, our results uncover a developmental gene regulatory network that is important for cardiac neural crest fate determination, with key factors reactivated during regeneration. SIGNIFICANCEMany common human congenital heart defects are linked to problems that arise during cardiac neural crest development. Here, we use the zebrafish, which has the remarkable ability to regenerate their adult heart, to understand the genetic programs that control cardiac development and adult repair. We discover a set of genes that control the development of the cardiac neural crest and find that these genes are reactivated after heart injury in the adult zebrafish. Unlike the zebrafish, human hearts have a very limited ability to regenerate after injury. Our findings in zebrafish can provide insight to potential clinical interventions for congenital heart defects and adult heart damage.

developmental biology↗

bioRxiv2022

Reconstructing the ancestral vertebrate brain using a lamprey neural cell type atlas

The vertebrate brain emerged more than [~]500 million years ago in common evolutionary ancestors. To systematically trace its cellular and molecular origins, we established a spatially resolved cell type atlas of the entire brain of the sea lamprey - a jawless species whose phylogenetic position affords the reconstruction of ancestral vertebrate traits - based on extensive single-cell RNA-seq and in situ sequencing data. Comparisons of this atlas to neural data from the mouse and other jawed vertebrates unveiled various shared features that enabled the reconstruction of the core cell type composition, tissue structures, and gene expression programs of the ancestral brain. However, our analyses also revealed key tissues and cell types that arose later in evolution. For example, the ancestral vertebrate brain was likely devoid of cerebellar cell types and oligodendrocytes (myelinating cells); our data suggest that the latter emerged from astrocyte-like evolutionary precursors on the jawed vertebrate lineage. Our work illuminates the cellular and molecular architecture of the ancestral vertebrate brain and provides a foundation for exploring its diversification during evolution.

evolutionary biology↗