Age and sex differences in the ventilatory response to hypoxia and hypercapnia in awake neonatal, pre-pubertal and young adult rats.

There is evidence for a "sensitive period" in respiratory development in rats around postnatal age (P) 12-13d. Little is known about sex differences during that time. The purpose of this study was to assess the effect of sex on breathing development, specifically around the "sensitive period". We used whole-body plethysmography to study breathing in normoxic, hypoxic and hypercapnic gases in non-anesthetized male and female neonatal rats from P10 to P15, juvenile (P30) and young adult (P90) rats. Compared to other neonatal ages, P12-13 male rats had significantly lower ventilation during normoxia, hypoxia, and hypercapnia. Compared to age-matched females, P12-13 male rats had lower ventilation in normoxia and hypoxia and a lower O(2) saturation during hypoxia. Circulating estradiol was greater in P12-13 male vs. female rats. Estradiol and ventilatory responses to hypoxia and hypercapnia were negatively correlated in neonatal male, but not female rats. Our results suggest that P10-15 includes a critical developmental period in male but not female rats.

Formation of the zebrafish midbrain-hindbrain boundary constriction requires laminin-dependent basal constriction.

The midbrain-hindbrain boundary (MHB) is a highly conserved fold in the vertebrate embryonic brain. We have termed the deepest point of this fold the MHB constriction (MHBC) and have begun to define the mechanisms by which it develops. In the zebrafish, the MHBC is formed soon after neural tube closure, concomitant with inflation of the brain ventricles. The MHBC is unusual, as it forms by bending the basal side of the neuroepithelium. At single cell resolution, we show that zebrafish MHBC formation involves two steps. The first is a shortening of MHB cells to approximately 75% of the length of surrounding cells. The second is basal constriction, and apical expansion, of a small group of cells that contribute to the MHBC. In the absence of inflated brain ventricles, basal constriction still occurs, indicating that the MHBC is not formed as a passive consequence of ventricle inflation. In laminin mutants, basal constriction does not occur, indicating an active role for the basement membrane in this process. Apical expansion also fails to occur in laminin mutants, suggesting that apical expansion may be dependent on basal constriction. This study demonstrates laminin-dependent basal constriction as a previously undescribed molecular mechanism for brain morphogenesis.