The influence of premature birth on laryngeal development for phonation.

INTRODUCTION: Dysphonia is a known consequence of premature birth, and is usually associated with endotracheal intubation in the neonatal period or surgical ligation of persistent patent ductus arteriosus. Recently, cases of dysphonia, in the absence of these causative factors, have been reported. OBJECTIVES: This review seeks to identify literature pertaining to those aspects of laryngeal development that may potentially be disrupted by premature birth. The purpose of the review is to determine whether there is any possible anatomical or physiological explanation for dysphonia to arose solely from premature birth. METHODS: This scoping review was conducted in accordance with the guidelines prescribed by Arskey and O'Malley (2005). Fifteen relevant papers were identified. Results were categorized into age-related categories, to identify changes in the developmental trajectory. Based on the results of the literature search, a further category of unphonated larynges was added. RESULTS: Potential differences in the laryngeal framework (e.g., the development of the cricoid cartilage and the shape of the glottis) and vocal fold histology, depending on gestational age and post-natal phonation were identified. Much literature focused on the macula flavae, however, the layers of the lamina propria were also discussed. DISCUSSION: It is unclear whether the process of differentiation of the layers of the lamina propria, which commences in the second to third months of life in term-born infants, is disrupted by prematurity. Further, development of the macula flavae continues until at least 28 weeks' gestation. Preterm children may not phonate immediately after birth, which may also affect laryngeal development.

Tyrosinase expression during neuroblast divisions affects later pathfinding by retinal ganglion cells.

Occulocutaneous albinism is caused by mutations in the gene encoding the enzyme tyrosinase. Individuals with this disorder are predisposed to visual system deficits. We determined the critical period during development when tyrosinase expression is essential for the appropriate pathfinding of ganglion cell axons from the retina to the dorsal lateral geniculate nucleus. We used a line of mice with a Tyrosinase transgene, the expression of which is regulatable with the lac operator-repressor system, to restrict tyrosinase activity to discrete periods of embryogenesis. When tyrosinase was expressed throughout the period of neuroblast divisions that produce the ipsilaterally projecting ganglion cells, axonal projections innervated the same volume of the ipsilateral dorsal lateral geniculate nucleus of the thalamus as in normal mice. If tyrosinase expression ceased before the end of neuroblast divisions, or was not initiated until after they had begun, the degree of ipsilateral innervation was smaller, as in albino mice. Tyrosinase expression was not required during the entire period of pathfinding itself or during final maturation of the retinogeniculate pathway. Thus, tyrosinase appears to set up a signal early in visual system development that determines the pathway taken later by ganglion cell axons.

Genetic interaction between expanded murine Hdh alleles and p53 reveal deleterious effects of p53 on Huntington's disease pathogenesis.

Huntingtin, the protein product of the Huntington's disease (HD) gene, is known to interact with the tumor suppressor p53. It has recently been shown that activation of p53 upregulates the level of huntingtin, both in vitro and in vivo, whereas p53 deficiency in HD-transgenic flies and mice has been found to be beneficial. To explore further the involvement of p53 in HD pathogenesis, we generated mice homozygous for a mutant allele of Hdh (HdhQ140) and with zero, one, or two functional alleles of p53. p53 deficiency resulted in a reduction of mutant huntingtin expression in brain and testis, an increase in proenkephalin mRNA expression and a significant increase in nuclear aggregate formation in the striatum. Because aggregation of mutant huntingtin is suggested to be a protective mechanism, both the increase in aggregate load and the restoration of proenkephalin expression suggest a functional rescue of at least several aspects of the HD phenotype by a deficiency in p53.