https://www.cell.com/cell/pdf/S0092-8674(06)01648-5.pdf

Trekking across the Brain: The Journey of Neuronal Migration

Neuronal migration is, along with axon guidance, one of the fundamental mechanisms underlying the wiring of the brain. As other organs, the nervous system has acquired the ability to grow both in size and complexity by using migration as a strategy to position cell types from different origins into specific coordinates, allowing for the generation of brain circuitries. Guidance of migrating neurons shares many features with axon guidance, from the use of substrates to the specific cues regulating chemotaxis. There are, however, important differences in the cell biology of these two processes. The most evident case is nucleokinesis, which is an essential component of migration that needs to be integrated within the guidance of the cell. Perhaps more surprisingly, the cellular mechanisms underlying the response of the leading process of migrating cells to guidance cues might be different to those involved in growth cone steering, at least for some neuronal populations.

/pdf/guiding-neuronal-cell-migrations-4z5sul9l23.pdf

Guiding Neuronal Cell Migrations

Members of the conserved Hedgehog (Hh) family of secreted proteins play fundamental roles during embryonic development and homeostasis of adult tissues. Hh signal transduction uses an unusual
 derepression mechanism, in which Hh binding to its receptor component Patched (Ptc) inhibits the capacity of Ptc to repress the heterotrimeric guanine nucleotide–binding protein–coupled
 receptor Smoothened (Smo). Activation of Smo is accomplished through phosphorylation and subcellular translocation from intracellular vesicles to the plasma membrane and, in vertebrates, also to
 the primary cilium. This Review focuses primarily on the signaling modules that are set in motion by binding of Hh to Ptc: the “canonical” pathway through which Smo promotes
 activation of the Gli family of transcription factors, the noncanonical type I pathway in which Ptc modulates cell proliferation and survival independently of Smo, and the noncanonical type II
 pathway by which Smo regulates the actin cytoskeleton through G inhibitory proteins and small guanosine triphosphatases.

The Hedgehog Signal Transduction Network

Reelin Regulates Cadherin Function via Dab1/Rap1 to Control Neuronal Migration and Lamination in the Neocortex

The development of the mammalian cerebellum is orchestrated by both cell-autonomous programs and inductive environmental influences. Here, we describe the main processes of cerebellar ontogenesis, highlighting the neurogenic strategies used by developing progenitors, the genetic programs involved in cell fate specification, the progressive changes of structural organization, and some of the better-known abnormalities associated with developmental disorders of the cerebellum.

/pdf/consensus-paper-cerebellar-development-if424wuguo.pdf

Consensus Paper: Cerebellar Development.

Nonreceptor protein tyrosine kinases of the Src family regulate the survival, proliferation, differentiation, and motility of many cell types, but their roles in brain development are unclear. Biochemical and in vitro experiments implicate Src and Fyn in the Reelin-dependent tyrosine phosphorylation of Dab1, which controls the positioning of radially migrating neurons in many brain regions. However, genetic evidence that either Src or Fyn mediates Reelin-dependent migrations in vivo has been lacking. Here, we report that, although Src is dispensable and although the absence of Fyn causes an intermediate phenotype, the combined absence of Src and Fyn almost abolishes tyrosine phosphorylation of Dab1 and causes defects in the fetal cortex and cerebellum very similar to those of dab1 mutants of the same age. Neurogenesis is not detectably affected, but the layering of neurons in the cortex is inverted, and the formation of the Purkinje plate is impaired. This implies that Src and Fyn are needed for Reelin-dependent events during brain development.

https://www.jneurosci.org/content/jneuro/25/37/8578.full.pdf

Gloria Kuo

Papers

Absence of Fyn and Src Causes a Reeler-Like Phenotype