Two experiments were conducted to assess the effect of genotype, production system, and nutrition on performance and livability of meat chickens for niche markets. Slow-growing (SG) and fast-growing genotypes (FG) were raised for 91 and 63 d, respectively, in experiment 1 (females) or 84 and 56 d, respectively, in experiment 2 (males). In each trial, SG were placed before FG to achieve a similar BW at processing. In experiment 1, each genotype was assigned to 8 pens of 20 birds each, with 4 pens within each genotype raised indoors in a conventional research facility or in a small facility with outdoor access. All birds were fed a low-nutrient diet. In experiment 2, genotype assignment to pens was as in experiment 1; however, 4 pens within each genotype were fed a low-nutrient diet or a conventional diet, and birds were raised indoors. Birds were gait-scored and commercially processed; legs were examined for tibial dyschon-droplasia lesions and scanned for bone mineral density. In experiment 1, FG gained more weight than SG (P < 0.05) even though they were placed later. Outdoor access increased feed intake, and feed efficiency was poorer (P< 0.05). Fast-growing genotypes had higher breast meat yield, whereas SG had higher wing and leg yields (P < 0.05). In experiment 2, the low-nutrient diet reduced (P< 0.05) gain of the SG; FG increased feed intake of the low-nutrient diet such that their gain was unaffected (P> 0.05). For FG, the low-nutrient diet resulted in a poorer (P < 0.05) feed efficiency. Although weight gain of the FG was maintained on the low-nutrient diet, breast yield was reduced (P < 0.05). Genotype affected bone health in both experiments, with SG having better gait scores and less tibial dyschondroplasia (P < 0.05). Outdoor access and the low-nutrient diet also resulted in better gait score (P < 0.05). These data indicate differences among genotypes and provide information about the efficiency and potential for alternative poultry systems.

1. The gait scoring system for broilers developed by Kestin et al. (Veterinary Record, 131: 190-194, 1992) has been widely used to evaluate leg problems. The many factors and measures associated with this scale have empirically established its external (biological) validity. However, published test-retest (within-observer) reliabilities are poor, and inter-observer reliabilities are unknown. We evaluated several modifications to this scale aimed at improving its objectivity and reliability. 2. Eighteen naïve observers scored a standardised video of birds exhibiting varying degrees of lameness, either using Kestin et al.'s system, or our modified system. 3. Test-retest reliability (0.906) for Kestin et al.'s system was higher than previously reported. Inter-rater reliability was also good (0.892). The modified system offered significantly better test-retest (0.948) and inter-rater reliabilities (0.943), without incurring costs in terms of time taken or difficulty of use. The systems were consistent, assigning individual birds the same score on average. 4. It is concluded that the modified system offers the advantages of reduced error within and between studies. 5. In a second experiment, we used our modified scoring system to examine the relationship between tibial dyschondroplasia (TD) and gait score in 267 selected broilers. 6. Neither the presence nor severity of TD affected gait score, suggesting that, at least in this strain of broilers, other leg problems like slipped tendons or torsional deformities had more influence on gait impairment than did TD.

Interlaminar astrocytes (ILA) in the cerebral cortex possess a soma in layer I and extend an interlaminar process that runs perpendicular to the pia into deeper cortical layers. We examined cerebral cortex from 46 species that encompassed most orders of therian mammalians, including 22 primate species. We described two distinct cell types with interlaminar processes that have been referred to as ILA, that we termed pial ILA and supial ILA. ILA subtypes differ in somatic morphology, position in layer I, and presence across species. We further described rudimentary ILA that have short GFAP+ processes that do not exit layer I, and “typical” ILA with longer GFAP+ processes that exit layer I. Pial ILA were present in all mammalian species analyzed, with typical ILA observed in Primates, Scandentia, Chiroptera, Carnivora, Artiodactyla, Hyracoidea, and Proboscidea. Subpial ILA were absent in Marsupialia, and typical subpial ILA were only found in Primate. We focused on the properties of pial ILA by investigating the molecular properties of pial ILA and confirming their astrocytic nature. We found that while the density of pial ILA somata only varied slightly, the complexity of ILA processes varied greatly across species. Primates, specifically bonobo, chimpanzee, orangutan, and human, exhibited pial ILA with the highest complexity. We showed that interlaminar processes contact neurons, pia, and capillaries, suggesting a potential role for ILA in the blood-brain barrier and facilitating communication among cortical neurons, astrocytes, capillaries, meninges, and cerebrospinal fluid.

Interlaminar astrocytes (ILAs) are a subset of cortical astrocytes that reside in layer I, express GFAP, have a soma contacting the pia, and contain long interlaminar processes that extend through several cortical layers. We studied the prenatal and postnatal development of ILAs in three species of primates (rhesus macaque, chimpanzee, and human). We found that ILAs are generated prenatally likely from radial glial (RG) cells, that ILAs proliferate locally during gestation, and that ILAs extend interlaminar processes during postnatal stages of development. We showed that the density and morphological complexity of ILAs increase with age, and that ILAs express multiple markers that are expressed by RG cells (Pax6, Sox2, and Nestin), specific to inner and outer RG cells (Cryab and Hopx), and astrocyte markers (S100β, Aqp4, and GLAST) in prenatal stages and in adult. Finally, we demonstrated that rudimentary ILAs in mouse also express the RG markers Pax6, Sox2, and Nestin, but do not express S100β, Cryab, or Hopx, and that the density and morphological complexity of ILAs differ between primate species and mouse. Together these findings contribute new information on astrogenesis of this unique class of cells and suggest a lineal relationship between RG cells and ILAs.

Neocortical astrogenesis follows neuronogenesis and precedes oligogenesis. Among key factors dictating its temporal articulation, there are progression rates of pallial stem cells (SCs) towards astroglial lineages as well as activation rates of astrocyte differentiation programs in response to extrinsic gliogenic cues. In this study, we showed that high Foxg1 SC expression antagonizes astrocyte generation, while stimulating SC self-renewal and committing SCs to neuronogenesis. We found that mechanisms underlying this activity are mainly cell autonomous and highly pleiotropic. They include a concerted downregulation of 4 key effectors channeling neural SCs to astroglial fates, as well as defective activation of core molecular machineries implementing astroglial differentiation programs. Next, we found that SC Foxg1 levels specifically decline during the neuronogenic-to-gliogenic transition, pointing to a pivotal Foxg1 role in temporal modulation of astrogenesis. Finally, we showed that Foxg1 inhibits astrogenesis from human neocortical precursors, suggesting that this is an evolutionarily ancient trait.

Varicose projection astrocytes (VP-As) are found in the cerebral cortex and have been described to be specific to humans and chimpanzees. To further examine the phylogenetic distribution of this cell type, we analyzed cortical tissue from several primates ranging from primitive primates to primates evolutionary closer to human such as apes. We specifically analyzed tissue from four strepsirrhine species, one tarsier, six species of platyrrhine monkeys, ten species of cercopithecoid monkeys, two hylobatid ape species, four to six cases each of chimpanzee, bonobo, gorilla, and orangutan, and thirteen human. We found that VP-As were present only in human and other apes (hominoids) and were absent in all other species. We showed that VP-As are localized to layer VI and the superficial white matter of the cortex. The presence of VP-As co-occured with interlaminar astrocytes that also had varicosities in their processes. Due to their location, their long tangential processes, and their irregular presence within species, we propose that VP-As are astrocytes that develop varicosities under specific conditions and that are not a distinct astrocyte type.

Glioblastoma is a devastating CNS tumour for which no cure is presently available. We wondered if manipulation of Emx2, which normally antagonizes cortico-cerebral astrogenesis by inhibiting proliferation of astrocyte progenitors, may be employed to counteract it. We found that Emx2 overexpression induced the collapse of seven out of seven in vitro tested glioblastoma cell lines. Moreover, it suppressed four out of four of these lines in vivo. As proven by dedicated rescue assays, the antioncogenic activity of Emx2 originated from its impact on at least six metabolic nodes, which accounts for the robustness of its effect. Finally, in two out of two tested lines, the tumor culture collapse was also achieved when Emx2 was driven by a neural stem cell-specific promoter, likely active within tumor-initiating cells. All that points to Emx2 as a novel, promising tool for therapy of glioblastoma and prevention of its recurrencies.

An alteration in the balance of excitation-inhibition has been proposed as a common characteristic of the cerebral cortex in autism, which may be due to an alteration in the number and/or function of the excitatory and/or inhibitory cells that form the cortical circuitry. We previously found a decreased number of the parvalbumin (PV)+ interneuron known as Chandelier (Ch) cell in the prefrontal cortex in autism. This decrease could result from a decreased number of Ch cells, but also from decreased PV protein expression by Ch cells. To further determine if Ch cell number is altered in autism, we quantified the number of Ch cells following a different approach and different patient cohort than in our previous studies. We quantified the number of Ch cell cartridges—rather than Ch cell somata—that expressed GAT1—rather than PV. Specifically, we quantified GAT1+ cartridges in prefrontal areas BA9, BA46, and BA47 of 11 cases with autism and 11 control cases. We found that the density of GAT1+ cartridges was decreased in autism in all areas and layers. Whether this alteration is cause or effect remains unclear but could result from alterations that take place during cortical prenatal and/or postnatal development.