Diversity of developing peripheral glia revealed by single-cell RNA sequencing.

The peripheral nervous system responds to a wide variety of sensory stimuli, a process that requires great neuronal diversity. These diverse neurons are closely associated with glial cells originating from the neural crest. However, the molecular nature and diversity among peripheral glia are not understood.

Netrin-1 Confines Rhombic Lip-Derived Neurons to the CNS.

During brainstem development, newborn neurons originating from the rhombic lip embark on exceptionally long migrations to generate nuclei important for audition, movement, and respiration. Along the way, this highly motile population passes several cranial nerves yet remains confined to the CNS. We found that Ntn1 accumulates beneath the pial surface separating the CNS from the PNS, with gaps at nerve entry sites.

Sequential Retraction Segregates SGN Processes during Target Selection in the Cochlea.

Unlabelled: A hallmark of the nervous system is the presence of precise patterns of connections between different types of neurons. Many mechanisms can be used to establish specificity, including homophilic adhesion and synaptic refinement, but the range of strategies used across the nervous system remains unclear. To broaden the understanding of how neurons find their targets, we studied the developing murine cochlea, where two classes of spiral ganglion neurons (SGNs), type I and type II, navigate together to the sensory epithelium and then diverge to contact inner hair cells (IHCs) or outer hair cells (OHCs), respectively.

Gata3 is a critical regulator of cochlear wiring.

Spiral ganglion neurons (SGNs) play a key role in hearing by rapidly and faithfully transmitting signals from the cochlea to the brain. Identification of the transcriptional networks that ensure the proper specification and wiring of SGNs during development will lay the foundation for efforts to rewire a damaged cochlea. Here, we show that the transcription factor Gata3, which is expressed in SGNs throughout their development, is essential for formation of the intricately patterned connections in the cochlea.

Sacral neural crest-derived cells enter the aganglionic colon of Ednrb-/- mice along extrinsic nerve fibers.

Both vagal and sacral neural crest cells contribute to the enteric nervous system in the hindgut. Because it is difficult to visualize sacral crest cells independently of vagal crest, the nature and extent of the sacral crest contribution to the enteric nervous system are not well established in rodents. To overcome this problem we generated mice in which only the fluorescent protein-labeled sacral crest are present in the terminal colon.

The intrinsic innervation of the lung is derived from neural crest cells as shown by optical projection tomography in Wnt1-Cre;YFP reporter mice.

Within the embryonic lung, intrinsic nerve ganglia, which innervate airway smooth muscle, are required for normal lung development and function. We studied the development of neural crest-derived intrinsic neurons within the embryonic mouse lung by crossing Wnt1-Cre mice with R26R-EYFP reporter mice to generate double transgenic mice that express yellow fluorescent protein (YFP) in all neural crest cells (NCCs) and their derivatives. In addition to utilizing conventional immunohistochemistry on frozen lung sections, the complex organization of lung innervation was visualized in three dimensions by combining the genetic labelling of NCCs with optical projection tomography, a novel imaging technique that is particularly useful for the 3D examination of developing organs within embryos.

Genetic association of the neuropilin-1 gene with type 1 diabetes in children: Neuropilin-1 expression in pancreatic islets.

Minor alleles of two SNPs in intron 9 of the NRP1 gene, which encodes neuropilin-1, were found to be associated with type 1 diabetes (T1D) in children. Neuropilin-1 peptides were confined to islets in human pancreas. This suggests neuropilins-1 could influence the development of some cases of T1D in children.

Age-dependent changes in the gut environment restrict the invasion of the hindgut by enteric neural progenitors.

The enteric nervous system (ENS) develops from neural crest cells (NCCs) that enter the foregut and hindgut to become enteric neural-crest-derived cells (ENCCs). When these cells of neural crest origin fail to colonize the terminal hindgut, this aganglionic region becomes non-functional and results in a condition in humans known as Hirschsprung's disease (HSCR). One of the genes associated with HSCR is endothelin receptor type B (Ednrb).

Targeting of endothelin receptor-B to the neural crest.

Endothelin receptor B (Ednrb) plays a critical role in the development of melanocytes and neurons and glia of the enteric nervous system. These distinct neural crest-derived cell types express Ednrb and share the property of intercalating into tissues, such as the intestine whose muscle precursor cells also express Ednrb. Such widespread Ednrb expression has been a significant obstacle in establishing precise roles for Ednrb in development.

Behavior of enteric neural crest-derived cells varies with respect to the migratory wavefront.

Neural crest-derived cells colonize the entire gastrointestinal tract. The migration of these enteric neural crest-derived cells (ENCCs) occurs by their formation of cellular strands that extend into the intestinal mesenchyme. We have studied the behavior of crest cells that underlies the formation and extension of these strands by time-lapse microscopy.

The pattern of neural crest advance in the cecum and colon.

Neural crest cells leave the hindbrain, enter the gut mesenchyme at the pharynx, and migrate as strands of cells to the terminal bowel to form the enteric nervous system. We generated embryos containing fluorescent enteric neural crest-derived cells (ENCCs) by mating Wnt1-Cre mice with Rosa-floxed-YFP mice and investigated ENCC behavior in the intact gut of mouse embryos using time-lapse fluorescent microscopy. With respect to the entire gut, we have found that ENCCs in the cecum and proximal colon behave uniquely.