Biology subjects

Fried, K.

Publications and source records attributed to Fried, K..

3 recordsLinked to original sources

bioRxiv2026

Single-cell, clonal and spatial atlases of cranial placodes illuminate their specification and evolution

The vertebrate head is defined by complex sensory structures derived from cranial placodes. Placodes arise alongside the neural crest at the neural plate border, yet the mechanisms governing their identity, diversification, and evolutionary origins are unclear. We present an integrated single-cell, spatial, and clonal atlas of placode development to resolve the dynamics of their lineage segregation. Combining single-cell RNA-sequencing, spatial transcriptomics, and high-resolution clonal tracing, we show that placodal and neighboring progenitors form a continuous transcriptional landscape with gradual transitions between domains. Domain boundary cells co-express markers of adjacent territories, suggesting transient bipotent states. Consistent with this, clonal analysis reveals sharing of progenitors between neighboring placodes, supporting a model of competitive segregation. Comparisons with amphioxus suggests that vertebrate olfactory placodes emerged from an ancestral neuroectoderm that later partitioned into distinct neural and olfactory domains. Our findings provide a unified framework for understanding the developmental and evolutionary origins of vertebrate sensory organs.

developmental biology↗

bioRxiv2023

Motor nerves direct the development of the sympathetic nervous system

The sympathetic nervous system controls a wide spectrum of bodily functions including operation of vessels, cardiac rhythm, and the "flight or fight response". Sympathetic neurons, which are neural crest-derived, develop in coordination with presynaptic motor nerves extending from the central nervous system (CNS). By using nerve-selective genetic ablations, we revealed that sympathetic ganglia development depends on CNS-derived motor innervation. In the absence of preganglionic motor nerves, trunk sympathetic chain ganglia were fragmented and smaller in size, while cervical ganglia were severely misshapen. Sympathetic neurons were misplaced along sensory fibers and projected towards abnormal paths, in some cases invading the sensory dorsal root ganglia. The misplaced progenitors of sympathoblasts corresponded to the nerve-associated, neural crest-derived Schwann cell precursors (SCPs). Notably, we found that SCPs activate the autonomic marker PHOX2B while migrating along motor nerves towards the region of the dorsal aorta in wildtype embryos, suggesting that SCP differentiate into sympathetic neurons while still nerve-associated in motor-ablated embryos. Ligand-receptor prediction from single cell transcriptomic data coupled with functional studies identified Semaphorin 3A/3F as candidate motor nerve-derived signals influencing neural crest migration along axons. Thus, motor nerves control the placement of sympathoblasts and their subsequent axonal navigation during critical periods of sympathetic chain development.

developmental biology↗

bioRxiv2019

Secondary ossification centers evolved to make endochondral bone growth possible under the weight-bearing demands of a terrestrial environment

Growth plate and articular cartilage constitute a single anatomical entity early in development, but later separate into two distinct structures by the secondary ossification center (SOC). The reason for such separation remains unknown. We found that evolutionarily SOC appears in animals conquering the land - amniotes. Analysis of ossification pattern in mammals with specialized extremities (whales, bats, jerboa) revealed that SOC development correlates with the extent of mechanical loads. Mathematical modelling revealed that SOC reduces mechanical stress within the growth plate. Functional experiments revealed high vulnerability of hypertrophic chondrocytes to mechanical stress and showed that SOC protects these cells from apoptosis caused by extensive loading. Atomic force microscopy showed that hypertrophic chondrocytes are the least mechanically stiff cells within the growth plate. Altogether, these findings suggest that SOC has evolved to protect the hypertrophic chondrocytes from the high mechanical stress encountered in the terrestrial environment.

evolutionary biology↗