Undergraduate neurobiology courses cover neural development as a major theme but there are few labs to provide hands-on experience with these topics. Here we share a 3-week set of lab activities using zebrafish embryos that allow students to see the direct effect of drug exposure on physical and emotional development. In these labs, student expose new embryos (Lab 1) to the environmental toxin lithium chloride, which inhibits anterior development and produces an eyeless phenotype in fixed larvae (Lab 2), and to psychiatric medications fluoxetine and quetiapine, which alter anxiety-like behavior measured live in grown juveniles (Lab 3). Lab worksheets ask students to investigate the signaling pathways affected by these drugs and how they might affect neural development in different ways. Student opinion surveys suggest these lab activities were successful in both providing hands-on work with zebrafish as a model organism for neural development and better understanding of how drugs can impact development of the nervous system.

Since their first description, the clustered protocadherins (cPcdhs) have sparked interest for their potential to generate diverse cell-surface recognition cues and their widespread expression in the nervous system. Through the use of mouse models, we have learned a great deal about the functions served by cPcdhs, and how their molecular diversity is regulated. cPcdhs are essential contributors to a host of processes during neural circuit formation, including neuronal survival, dendritic and axonal branching, self-avoidance and targeting, and synapse formation. Their expression is controlled by the interplay of epigenetic marks with proximal and distal elements involving high order DNA looping, regulating transcription factor binding. Here, we will review various mouse models targeting the cPcdh locus and how they have been instructive in uncovering the regulation and function of the cPcdhs.

Human brain development is an intricate process that involves precisely timed coordination of cell proliferation, fate specification, neuronal differentiation, migration, and integration of diverse cell types. Understanding of these fundamental processes, however, has been largely constrained by limited access to fetal brain tissue and the inability to prospectively study neurodevelopment in humans at the molecular, cellular and system levels. Although non-human model organisms have provided important insights into mechanisms underlying brain development, these systems do not fully recapitulate many human-specific features that often relate to disease. To address these challenges, human brain organoids, self-assembled three-dimensional neural aggregates, have been engineered from human pluripotent stem cells to model the architecture and cellular diversity of the developing human brain. Recent advancements in neural induction and regional patterning using small molecules and growth factors have yielded protocols for generating brain organoids that recapitulate the structure and neuronal composition of distinct brain regions. Here, we first provide an overview of early mammalian brain development with an emphasis on molecular cues that guide region specification. We then focus on recent efforts in generating human brain organoids that model the development of specific brain regions and highlight endeavors to enhance the cellular complexity to better mimic the in vivo developing human brain. We also provide examples of how organoid models have enhanced our understanding of human neurological diseases and conclude by discussing limitations of brain organoids with our perspectives on future advancements to maximize their potential.

The hindbrain develops through a process of segmentation which is coupled with the ordered expression of Hox genes to generate regional diversity of key neural and craniofacial derivatives during head development. This is a fundamental feature governed by a gene regulatory network conserved to the base of vertebrate evolution.

This study tested the effect of early neglect on defensive and appetitive physiology during puberty. Emotion-modulated reflexes, eye-blink startle (defensive) and postauricular (appetitive), were measured in 12-to-13-year-old internationally adopted youth (from foster care or from institutional settings) and compared to non-adopted US born controls. Startle Reflex: adopted youth displayed lower overall startle amplitude across all valences and startle potentiation to negative images was negatively related to severity of pre-adoption neglect. Postauricular reflex (PAR): adopted youth showed larger PAR magnitude across all valences. Puberty: adopted youth showed diminished PAR potentiation to positive images and startle potentiation during mid/late puberty versus the opposite pattern in not-adopted. Early neglect was associated with blunted fast defensive reflexes and heightened fast appetitive reflexes. After puberty, early neglected youth showed physiological hyporeactivity to threatening and appetitive stimuli versus heightened reactivity in not adopted youth. Behavioral correlates in this sample and possible neurodevelopmental mechanisms of psychophysiological differences are discussed.