Highlights in DD

Abstract

“Highlights” calls attention to exciting advances in developmental biology that have recently been reported in Developmental Dynamics. Development is a broad field encompassing many important areas. To reflect this fact, the section spotlights significant discoveries that occur across the entire spectrum of developmental events and problems: from new experimental approaches, to novel interpretations of results, to noteworthy findings utilizing different developmental organisms. Repressed identities (Brn3a Regulates the Transition From Neurogenesis to Terminal Differentiation and Represses Non-neural Gene Expression in the Trigeminal Ganglion by Jason Lanier, Iain M. Dykes, Stephanie Nissen, S. Raisa Eng, and Eric E. Turner, Dev Dyn 238:3065–3079). The word “repress” often has a negative connotation. Think “repressed memories,” or “repressed dissidents.” Here, Lanier et al. demonstrate that repression can also be used for good. The homeodomain transcription factor Brn3a is a transcriptional repressor required for differentiation of sensory neurons in the trigeminal ganglia (TG). To understand regulatory mechanisms by which the gene exerts its effects, the authors used microarray analysis to compare wild-type vs. Brn3a−/− TG during the initial stages of differentiation (E11.5–E13.5). Mutant mice display prolonged expression of genes associated with neural progenitors and cell proliferation, and reduced expression of neural differentiation markers—all signs of developmental delay. Unexpectedly, Brn3a−/− TG also express markers specific to cardiac cells or cranial mesoderm, although the neuronal cells do not terminally differentiate as these foreign cell types. Results were confirmed with reverse transcriptase-polymerase chain reaction and in situ hybridization. The connection between TG and cardiac cell types may stem from a common precursor—they both derive from cranial neural crest—or from a partly overlapping program of gene expression activated by the transcription factor Islet1, which is expressed in both cell types. Understanding the molecular programs that tether the disparate cell types may help illuminate the logic behind using repressors to exercise developmental cell fate decisions, and may be useful for clinical stem cell applications. Becoming long and lean (Morphogenesis of the Primitive Gut Tube Is Generated by Rho/ROCK/Myosin II–Mediated Endoderm Rearrangements by Rachel A. Reed, Mandy A. Womble, Michel K. Dush, Rhesa R. Tull, Stephanie K. Bloom, Allison R. Morckel, Edward W. Devlin, and Nanette M. Nascone-Yoder, Dev Dyn 238:3111–3125). Here, Reed and colleagues present the secrets to becoming long and lean—fast. In the course of just 1 day, the Xenopus primitive gut tube (PGT), the precursor to the gastrointestinal tract, morphs from something akin to a dense, rotund gnocchi to a hollow, lithe bucatini, lengthening more than three-fold in the process. How does the PGT do it? To find out, the authors used immunohistochemistry to examine cell shape, and positioning of basement membrane and nuclei in the maturing PGT. Over time, cells move radially toward the PGT circumference, intercalate between anterior and posterior neighbors, and polarize. The process not only thins the tube from 4–5 cell layers to one, but also elongates it. At the molecular level, they find that Rho GTPase and the Rho effectors Rho associated kinase (ROCK) and nonmuscle Myosin II are required for PGT cell polarization and adhesion. Inhibition of Rho signaling prevents gut lengthening and narrowing, maintaining the original gnocchi shape. The authors note that processes that shape the maturing PGT are analogous to a modified version of tissue elongation events that occur during elongation. The secret is out. Defining intestinalization (Dynamic Patterning at the Pylorus: Formation of an Epithelial Intestine–Stomach Boundary in Late Fetal Life by Xing Li, Aaron M. Udager, Chunbo Hu, Xiaotan T. Qiao, Neil Richards, and Deborah L. Gumucio, Dev Dyn 238:3205–3217). When a single event makes a significant impact on the surrounding environment, it is worthy of its own terminology. Here, Li and colleagues identify such an event. To determine molecular mechanisms that functionally segregate organs of the gastrointestinal tract (esophagus, stomach, small and large intestines), the authors carry out sophisticated microarray analyses comparing gene expression in the posterior stomach—the pylorus—and the adjacent anterior small intestine—the duodenum—over time. Pylorus and duodenum transcriptomes are relatively similar at embryonic day (E) 14.5, a time during which stomach (Sox2) and intestine (Cdx2) markers are expressed, but with diffuse boundaries. At E16.5, the transcriptomes vary considerably, and particularly large changes occur within the duodenum over time. Further analyses show that the bulk of up-regulated duodenal genes are epithelial, including those that confer organ-defining metabolic and absorption functions. In situ hybridization results confirm that E16.5 is a critical stage when differentially expressed genes create sharp boundaries between the pylorus and duodenum. In addition, expression of Shh pathway effectors, previously shown to be important for intestinal differentiation, significantly decrease in the E16.5 duodenum. Thus, the authors coin the new term intestinalization, defining the process by which the duodenum epithelia unleashes an onslaught of functional differentiation genes, setting it apart from the rest of the gastrointestinal tract.