Cortical development depends on the active integration of cell autonomous and extrinsic cues, but the coordination of these processes is poorly understood. Here, we show that the apical complex protein Pals1 and Pten have opposing roles in localizing the Igf1R to the apical, ventricular domain of cerebral cortical progenitor cells. We found that the cerebrospinal fluid (CSF), which contacts this apical domain, has an age-dependent effect on proliferation, much of which is attributable to Igf2, but that CSF contains other signaling activities as well. CSF samples from patients with glioblastoma multiforme show elevated Igf2 and stimulate stem cell proliferation in an Igf2-dependent manner. Together, our findings demonstrate that the apical complex couples intrinsic and extrinsic signaling, enabling progenitors to sense and respond appropriately to diffusible CSF-borne signals distributed widely throughout the brain. The temporal control of CSF composition may have critical relevance to normal development and neuropathological conditions.

Objective To describe differences in outcomes between pregnant women with and without coronavirus dsease 2019 (COVID-19). Design Prospective cohort study of pregnant women consecutively admitted for delivery, and universally tested via nasopharyngeal (NP) swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using reverse transcription-polymerase chain reaction. All infants of mothers with COVID-19 underwent SARS-CoV-2 testing. Setting Three New York City hospitals. Population Pregnant women >20 weeks of gestation admitted for delivery. Methods Data were stratified by SARS-CoV-2 result and symptomatic status, and were summarised using parametric and nonparametric tests. Main outcome measures Prevalence and outcomes of maternal COVID-19, obstetric outcomes, neonatal SARS-CoV-2, placental pathology. Results Of 675 women admitted for delivery, 10.4% were positive for SARS-CoV-2, of whom 78.6% were asymptomatic. We observed differences in sociodemographics and comorbidities among women with symptomatic COVID-10 versus asymptomatic COVID-19 versus no COVID-19. Caesarean delivery rates were 46.7% in symptomatic COVID-19, 45.5% in asymptomatic COVID-19 and 30.9% in women without COVID-19 (P = 0.044). Postpartum complications (fever, hypoxia, readmission) occurred in 12.9% of women with COVID-19 versus 4.5% of women without COVID-19 (P < 0.001). No woman required mechanical ventilation, and no maternal deaths occurred. Among 71 infants tested, none were positive for SARS-CoV-2. Placental pathology demonstrated increased frequency of fetal vascular malperfusion, indicative of thrombi in fetal vessels, in women with COVID-19 versus women without COVID-19 (48.3% versus 11.3%, P < 0.001). Conclusion Among pregnant women with COVID-19 at delivery, we observed increased caesarean delivery rates and increased frequency of maternal complications in the postpartum period. Additionally, intraplacental thrombi may have maternal and fetal implications for COVID-19 remote from delivery.

Many living organisms track light sources and halt their movement when alignment is achieved. This phenomenon, known as phototropism, occurs, for example, when plants self-orient to face the sun throughout the day. Although many artificial smart materials exhibit non-directional, nastic behaviour in response to an external stimulus, no synthetic material can intrinsically detect and accurately track the direction of the stimulus, that is, exhibit tropistic behaviour. Here we report an artificial phototropic system based on nanostructured stimuli-responsive polymers that can aim and align to the incident light direction in the three-dimensions over a broad temperature range. Such adaptive reconfiguration is realized through a built-in feedback loop rooted in the photothermal and mechanical properties of the material. This system is termed a sunflower-like biomimetic omnidirectional tracker (SunBOT). We show that an array of SunBOTs can, in principle, be used in solar vapour generation devices, as it achieves up to a 400% solar energy-harvesting enhancement over non-tropistic materials at oblique illumination angles. The principle behind our SunBOTs is universal and can be extended to many responsive materials and a broad range of stimuli.

SUMMARY Microcephaly is a neurodevelopmental disorder causing significantly reduced cerebral cortex size. Many known microcephaly gene products localize to centrosomes, regulating cell fate and proliferation. Here, we identify and characterize a nuclear zinc finger protein, ZNF335/NIF-1, as a causative gene for severe microcephaly, small somatic size, and neonatal death. Znf335-null mice are embryonically lethal and conditional knockout leads to severely reduced cortical size. RNA-interference and postmortem human studies show that Znf335 is essential for neural progenitor self-renewal, neurogenesis, and neuronal differentiation. ZNF335 is a component of a vertebrate-specific, trithorax H3K4-methylation complex, directly regulating REST/NRSF, a master regulator of neural gene expression and cell fate, as well as other essential neural-specific genes. Our results reveal ZNF335 as an essential link between H3K4 complexes and REST/NRSF, and provide the first direct genetic evidence that this pathway regulates human neurogenesis and neuronal differentiation.

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Cellular morphology is an essential determinant of cellular function in all kingdoms of life, yet little is known about how cell shape is controlled. Here we describe a molecular program that controls the early morphology of neurons through a metazoan-specific zinc finger protein, Unkempt. Depletion of Unkempt in mouse embryos disrupts the shape of migrating neurons, while ectopic expression confers neuronal-like morphology to cells of different nonneuronal lineages. We found that Unkempt is a sequence-specific RNA-binding protein and identified its precise binding sites within coding regions of mRNAs linked to protein metabolism and trafficking. RNA binding is required for Unkempt-induced remodeling of cellular shape and is directly coupled to a reduced production of the encoded proteins. These findings link post-transcriptional regulation of gene expression with cellular shape and have general implications for the development and disease of multicellular organisms.