Callejas-Marin, A. | Search bioRxiv

bioRxiv2025

TFAP2A+ embryonic progenitor cells undergo fate diversification to give rise to human amnion, germline, and mesoderm

Amnion, germline and mesoderm specification at the posterior end of the human embryo occur around the same time in vivo. Similarly, in vitro generation of germline and amnion is associated with mesoderm induction regardless of differentiation platform. Yet, the lineage relationships between amnion, germline and mesoderm remains unresolved. By adding Basement Membrane Extract (BME) to the media, we demonstrate emergence of TFAP2A+/SOX2-epithelial progenitor cells which develop in response to BMP receptor signaling. We track the order of embryonic events that take place from this progenitor pool revealing that amnion-like cells (AMLCs) and primordial germ cell (PGC)-like cells (PGCLCs) are specified first. Shortly after, gastrulating mesoderm-like cells (MeLCs) arise that undergo an epithelial to mesenchymal transition (EMT). These results highlight the interconnected role of basement membrane deposition and BMP receptor signaling in the specification of human germline, amnion and mesoderm from TFAP2A+ embryonic progenitors.

developmental biology↗

bioRxiv2023

Projection neurons are necessary for the maintenance, but not for the assembly, of the mouse olfactory circuit

The assembly and maintenance of neural circuits is crucial for proper brain function. Although the assembly of brain circuits has been extensively studied, much less is understood about the mechanisms controlling their maintenance as animals mature. In the olfactory system, the axons of olfactory sensory neurons (OSNs) expressing the same odor receptor converge into discrete synaptic structures of the olfactory bulb (OB) called glomeruli, forming a stereotypic odor map. The OB projection neurons, called mitral and tufted cells (M/Ts), have a single dendrite that branches into a single glomerulus, where they make synapses with OSNs. We used a genetic method to progressively eliminate the vast majority of M/T cells in early postnatal mice, and observed that the assembly of the OB bulb circuits proceeded normally. However, as the animals became adults the apical dendrite of remaining M/Ts grew multiple branches that innervated several glomeruli, and OSNs expressing single odor receptors projected their axons into multiple glomeruli, disrupting the olfactory sensory map. Moreover, ablating the M/Ts in adult animals also resulted in similar structural changes in the projections of remaining M/Ts and axons from OSNs. Interestingly, the ability of these mice to detect odors was relatively preserved despite only having 1-5% of projection neurons transmitting odorant information to the brain, and having highly disrupted circuits in the OB. These results indicate that a reduced number of projection neurons does not affect the normal assembly of the olfactory circuit, but induces structural instability of the olfactory circuitry of adult animals.

neuroscience↗