During development, neural precursors migrate in response to positional cues such as growth factor gradients. However, the mechanisms that enable precursors to sense and respond to such gradients are poorly understood. Here we show that cerebellar granule cell precursors (GCPs) migrate along a gradient of brain-derived neurotrophic factor (BDNF), and we demonstrate that vesicle trafficking is critical for this chemotactic process. Activation of TrkB, the BDNF receptor, stimulates GCPs to secrete BDNF, thereby amplifying the ambient gradient. The BDNF gradient stimulates endocytosis of TrkB and associated signaling molecules, causing asymmetric accumulation of signaling endosomes at the subcellular location where BDNF concentration is maximal. Thus, regulated BDNF exocytosis and TrkB endocytosis enable precursors to polarize and migrate in a directed fashion along a shallow BDNF gradient.

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BACKGROUND Children with food allergy have been shown to have increased small intestinal permeability (IP) following ingestion of the offending food as well as during elimination diets. We investigated IP in asymptomatic food-allergic children during an elimination diet to identify clinical characteristics associated with altered IP. METHODS Urinary recovery ratios of lactulose and mannitol (L/M) were determined five hours following ingestion of 7.5 g of lactulose and 2 g of mannitol in 131 cow’s milk- and egg-allergic children. An L/M ratio of ≥0.025 was considered abnormal based upon previously established laboratory internal references. A chart review was conducted to assess the clinical characteristics of these patients. RESULTS A total of 50 (38%) of the 131 children (median 6.7, range 4.8 – 8.9 years); 66.2% male) with food allergy had elevated IP while asymptomatic on strict elimination diets. Age and height negatively correlated with IP. However, in the regression model analysis, abnormal IP was associated with shorter stature independently of age. Otherwise, food allergic patients with increased IP were comparable in gender, nutritional status, age of onset of food allergy, history of reactions, atopic diseases and family history of food allergies to those with normal IP. CONCLUSIONS Elevated IP was found in about one-third of asymptomatic food-allergic children on elimination diets and was associated with shorter stature. Our results suggest that increased IP may be an intrinsic trait in a subset of food allergic children. However, large, prospective studies are necessary to determine the role of impaired intestinal barrier in food allergy.

Pediatric providers are encouraged to ask adolescents and young adults with SHCN about their understanding of, and engagement in, health risk behaviors. A multidisciplinary approach to encourage a healthy lifestyle within this population may have significant health benefits.